Abstract
In the nervous system, Netrin-1 serves as a neural guide, mediating the neuronal development. However, it remains blurred whether Netrin-1 can protect neurons from apoptosis induced by cerebral stroke. In the current study, the cultured rat primary cortical neurons were transfected with Netrin-1-encoding lentivirus before the oxygen-glucose-deprivation (OGD) treatment. Cell death and apoptosis were evaluated by lactate dehydrogenase (LDH) release and flow cytometry. We found that Netrin-1 attenuated OGD-induced cell death and neuronal apoptosis at 24 h after OGD treatment, and that the overexpression of Netrin-1 activated the ERK signaling pathway. These effects were partly abolished by blocking its receptor deleted in colorectal cancer (DCC) or U0126, an inhibitor of the ERK signaling pathway. Netrin-1 overexpression in neurons elevated the expression of DCC, on mRNA level and protein level. Netrin-1 also reduced DNA damage. Taken together, our findings suggest that Netrin-1 attenuates cell death and neuronal apoptosis via the DCC/ERK signaling pathway in the cultured primary cortical neurons after OGD injury, which may involve the mediation of DNA damage in the neurons.
Highlights
Cerebral stroke often features the occlusion or hemorrhage of cerebral vessels and results in physical dysfunction or even death of the organisms
We found that Netrin-1 attenuated OGD-induced cell death and neuronal apoptosis and that the overexpression of Netrin-1 activated the ERK signaling pathway
In the Lv-Nnt-1 group, the phosphorylation of ERK was increased in OGD condition but not in normal condition, which indicated that Netrin-1 induced ERK phosphorylation in the primary cortical neurons after OGD (0.91 ± 0.032 vs. 0.57 ± 0.030, p < 0.05)
Summary
Cerebral stroke often features the occlusion or hemorrhage of cerebral vessels and results in physical dysfunction or even death of the organisms. Netrin-1, as a guide in neuronal migration, attracts axons towards the middle of spinal cord, which is mediated by deleted in colorectal cancer (DCC; Forcet et al, 2002), and promotes neurogenesis in the striatal primordium (Hamasaki et al, 2001). It plays a chemorepulsive role in axons of trochlear, trigeminal and facial nerves, which is mediated by Unc5-related proteins (Yung et al, 2015).
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